Person:
Reinhold, Bruce

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Reinhold

First Name

Bruce

Name

Reinhold, Bruce
Author's Publications: search.filters.isAuthorOfPublication.ed239513-853a-4903-ac23-43b09dadc571

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Forward Vaccinology: CTL Targeting Based upon Physical Detection of HLA-Bound Peptides
    (Frontiers Media S.A., 2014) Reinherz, Ellis; Keskin, Derin Benerci; Reinhold, Bruce
    Vaccine-elicited cytotoxic T lymphocytes (CTL) recognizing conserved fragments of a pathogen’s proteome could greatly impact infectious diseases and cancers. Enabling this potential are recent advances in mass spectrometry that identify specific target peptides among the myriad HLA-bound peptides on altered cells. Ultrasensitivity of these physical detection methods allows for the direct assessment of peptide presentation on small numbers of tissue-derived cells. In addition, concurrent advances in immunobiology suggest ways to induce CTLs with requisite functional avidity and tissue deployment. Elicitation of high-avidity resident-memory T cells through vaccination may shift the vaccinology paradigm both for preventive and therapeutic approaches to human disease control.
  • Thumbnail Image
    Publication
    Direct Identification of an HPV-16 Tumor Antigen from Cervical Cancer Biopsy Specimens
    (Frontiers Research Foundation, 2011) Keskin, Derin Benerci; Reinhold, Bruce; Lee, Sun Young; Zhang, Guanglan; Lank, Simon; O’Connor, David H.; Berkowitz, Ross; Brusic, Vladimir; Kim, Seung Jo; Reinherz, Ellis
    Persistent infection with high-risk human papilloma viruses (HPV) is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile, and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altered epithelium, we exploited Poisson detection mass spectrometry (MS\(^3\)) to identify those epitopes and inform future T cell-based vaccine design. Nine cervical cancer biopsies from HPV-16 positive HLA-A*02 patients were obtained, histopathology determined, and E7 oncogene PCR-amplified from tumor DNA and sequenced. Conservation of E7 oncogene coding segments was found in all tumors. MS\(^3\) analysis of HLA-A*02 immunoprecipitates detected E7\(_{11–19}\) peptide (YMLDLQPET) in seven of the nine tumor biopsies. The remaining two samples were E7\(_{11–19}\) negative and lacked the HLA-A*02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A*02 alleles. Thus, the conserved E7\(_{11–19}\) peptide is a dominant HLA-A*02 binding tumor antigen in HPV-16 transformed cervical squamous and adenocarcinomas. Findings that a minority of HLA-A*02:01 tumors lack expression of both E7\(_{11–19}\) and a peptide from a thioreductase important in processing of cysteine-rich proteins like E7 underscore the value of physical detection, define a potential additional tumor escape mechanism and have implications for therapeutic cancer vaccine development.